A Benzoic Acid Terpyridine-Based Cyclometalated Iridium(Iii) Complex As a Two-Photon Fluorescence Probe for Imaging Nuclear Hist

ChemComm COMMUNICATION A benzoic acid terpyridine-based cyclometalated iridium(III) complex as a two-photon fluorescence Cite this: Chem. Commun., 2018, 54, 3771 probe for imaging nuclear histidine† Received 2nd February 2018, a a ab c d Accepted 14th March 2018 Qiong Zhang, ‡ Xin Lu, ‡ Hui Wang, ‡ Xiaohe Tian, * Aidong Wang, Hongping Zhou, a Jieying Wu a and Yupeng Tian *ae DOI: 10.1039/c8cc00908b rsc.li/chemcomm A series of two-photon active cyclometalated iridium(III) complexes include reduced photobleaching, autofluorescence, non-invasive (Ir1, Ir2 and Ir3) were designed. Ir1 with a two-photon action cross- excitation, and deeper tissue penetration.8–10 However, two- section of 40 GM in the NIR region has been developed for photon absorption (2PA) materials with moderate two-photon targeting intracellular histidine. Two-photon micrographs showed absorption cross-section (s) values usually possess extended that Ir1 could rapidly and selectively light up the nucleus in both p-conjugated planar structures, consequently leading to the use fixed and live cells and is capable of displaying nuclear histidine of biologically unfriendly solvents (e.g. DMSO). Therefore, the distribution in ultra-detail using a super resolution (SR) technique design and synthesis of novel fluorescent probes with histidine under stimulated emission depletion (STED) microscopy. specificity still remain a challenge.11 Recently, the use of precious-metal complexes such as Ru(II), Among the twenty amino acids, histidine is active in maintaining Ir(III) and Pt(II) as luminescent probes has attracted increasing healthy tissues and protecting nerve cells that transport messages interest due to their advantageous photophysical properties and 1,2 12 from the brain to the various other parts of the body. While in low toxicity. Among them, cyclometalated iridium(III)complexes living cells, histidine acts as a structural protein that closely have gained increasing attention in the development of sub- associates with DNA and is known to lead to a variety of ailments cellular location agents or bio-probes due to their unique such as asthma and advanced liver cirrhosis.3 Hence the develop- photophysical properties including large Stokes shifts and high 13 ment of high-quality methods for histidine detection is extremely photostability. To date, iridium(III)-complexes for detecting necessary. Numerous studies have dealt with the detection histidine (His) have rarely been reported.14 And most of these 4 of histidine using techniques such as voltammetry, UV/vis cyclometalated iridium(III) complexes only have a tendency to spectroscopy,5 luminescence spectroscopy methods6 and fluores- be localized in mitochondria.15 In this work, we report a series of 7 cence spectroscopy. However, most of the available probes cyclometalated iridium(III)complexes(Ir1–Ir3) for the purpose of exhibit poor selectivity or require sophisticated detection systems nuclear histidine targeting. Considerations including the photo- such as the use of organic solvents. The development of reliable, physical properties and intracellular behaviour are listed as rapid and accurate methods for the determination of histidine is follows: (1) the Ir–C bond, constructed by 2-phenyl pyridine, was still a highly challenging area. At present, visualization of intra- used to stabilize the energy levels of the Ir complexes. Subsequently, cellular histidine under two-photon microscopy (2PM) is an the two-photon absorption (2PA) activity was tuned using terpyridine attractive approach. The advantages of two-photon excitation derivatives, owing to their strong electron-withdrawing ability, moderate p-conjugated system and strong binding affinity 11 a Department of Chemistry, Key Laboratory of Functional Inorganic Material toward most metal ions. (2) Compared to those in our Chemistry of Anhui Province, Anhui University, Hefei 230601, P. R. China. previous work,11,16 the newly introduced carboxylic acid group E-mail: [email protected] can further influence the extent of electron delocalization and b Department of Chemistry, Wannan Medical College, Wuhu 241002, P. R. China c School of Life Science, Anhui University, Hefei 230601, P. R. China. increase the solubility of the complexes, as well as provide good E-mail: [email protected] biocompatibility. Furthermore, the carboxylic acid group might d School of Chemistry and Chemical Engineering, Huangshan University, accelerate penetration of the iridium(III) complex (Ir1) across Huangshan, P. R. China the nuclear membrane and the phenanthroline group with e State Key Laboratory of Coordination Chemistry, Nanjing University, its excellent planarity can connect with histidine. (3) The Nanjing 210093, P. R. China † Electronic supplementary information (ESI) available. CCDC 1585448. For ESI and additional pyridine ring can provide a lone electron pair, which crystallographic data in CIF or other electronic format see DOI: 10.1039/c8cc00908b could easily be protonated and might lead to good water- ‡ These authors contributed equally to this work. solubility. In addition, the pyridine ring possibly forms a This journal is © The Royal Society of Chemistry 2018 Chem. Commun., 2018, 54, 3771--3774 | 3771 Communication ChemComm Scheme 1 The molecular structure of the Ir(III) complex (Ir1). hydrogen bond with histidine to stabilize the molecule in vivo and in vitro (Scheme 1). The synthesis procedures for Ir1–Ir3 areoutlinedinSchemeS1 (ESI†). The crystal structure information reveals that the Fig. 1 (a) Emission spectra of Ir1 (20 mM) with various amino acids [such iridium(III) centre in Ir2 adopts a distorted octahedral geometry as Ala, Arg, Asn, Gln, Glu, Gly, GSH, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, (Scheme S1, ESI†). One of the pyridine rings was not coordi- Trp, Tyr, Val, Cys, Hcy], ct-DNA, RNA and BSA in PBS buﬀer (pH = 7.4). (b) Changes in the luminescence emission spectra of Ir1 (20 mM) with nated to the Ir1(III) centre indicating that the extra free pyridine 11a,16 various amounts of histidine (0–14 equiv.) in PBS buffer. (c) Two-photon moiety is prone to targeting subcellular organelles. The action cross sections of Ir1 in the presence or absence of His in PBS buffer. linkage between the two planes was conjugated with bond (d) The frontier molecular orbital distributions of Ir1-His. (e) The models lengths of 1.439 Å (C00B–C00H) and 1.452 Å (C00S–C019) for obtained after molecular modeling of the interaction of Ir1 with His. Ir2, revealing that the bond length of C–C is located between that of a normal CQC double bond (1.32 Å) and a C–C single bond (1.53 Å). Notably, there is an active hydrogen atom prone 593 nm when it is excited at 405 nm. The interactions of Ir1 to dissociation and a higher degree of electron delocalization in with numerous intracellular substances including amino acids, the carboxyl group (Fig. S7, ESI†), which caused a nonlinear proteins, DNA and RNA were examined by one and two-photon optical response,17 as well as it maybe being sensitive to amino fluorescence experiments. Only histidine and BSA (a histidine- acids in living cells. The triplet Ir(III) complexes for use in two- rich protein) triggered a significant luminescence enhancement. photon processes require efficient intersystem crossing (ISC), Upon addition of increased concentrations of histidine (Fig. 1(a) large Stokes shifts and relatively long-lived triplet excited state and (b)), a new emission at 493 nm appeared and the intensity lifetimes.18,19 The band at 475 nm is assigned to a p*(C–N) - increase corresponded to a blue shift of 100 nm. The phosphor- p*(L) ligand-to-ligand charge-transfer (LLCT) transition, prob- escence intensity of Ir1 at 493 nm (F o 1%, t = 37.55 ns) was ably mixed with some 3MLCT contribution (Fig. S4(a), ESI†). enhanced up to 27-fold when the concentration of histidine was The temperature-dependent shifts of the emission are typical of increased from 0 to 280 mM(F = 4.81%, t = 97.88 ns). The MLCT phosphorescence (Fig. S4(b), ESI†), arising from the significant enhancement of the phosphorescence quantum yield different environments surrounding the molecule associated suggests that Ir1 is suitable for use in aqueous media. These with stabilization of the polar MLCT emissive state. To support results indicate that Ir1 displays high selectivity for histidine/ the experimentally determined photophysical properties, TDDFT histidine-containing proteins in vitro. To explore the potential calculations showed that the lowest-lying triplet state (T1)is of Ir1 for 2PFM applications, the histidine induced obvious mainly described by the HOMO - LUMO excitation and has a enhancement of the 2PEF of Ir1, corresponding to that of one- 3 3 MLCT/ LLCT nature. The second lowest state (T2), which also has photon excited fluorescence (1PEF) (Fig. S12, ESI†), was inves- 3 3 a MLCT/ LLCT nature, appears B0.3 eV higher in energy than T1 tigated. In addition, two-photon absorption action cross sections and presents some 3LC character due to excitations centred on the (Fs) were further calculated to evaluate the two-photon activity ligand. These transitions are in keeping with the experimental of Ir1 and Ir-His (Fig. 1(c) and Fig. S12, ESI†). The Fs of Ir1 at results, which are attributed to two classes of transition (Fig. S4(c) 780 nm increased from 40 GM to 48 GM (Ir1-His). This result and Table S2, ESI†). indicates that Ir1 undergoes distinct changes in two-photon The 2PA action cross-section (dmax)ofIr1 in DMSO/water activity before and after reacting with His, which implies that (DMSO : H2O = 1 : 9) is presented in Fig. S4(d) (ESI†) and Ir1 is suitable for tracking histidine using the 2PFM technique. Fig. 1(c). The largest 2PA action cross-sections of Ir complexes To verify the above sensing mechanism, 1H NMR titration were located around 780 Æ 20 nm with dmax values between experiments were carried out in d6-DMSO : D2O = 9 : 1 (v/v).

Load more